The growth of epithelial tumors is often governed by cell interactions with the surrounding stroma. Drosophila has been instrumental in identifying the relevant molecular elements mediating these interactions. Of note is the role of the TNF ligand Eiger, released from recruited blood cells, in activating the JNK tumor-promoting pathway in epithelial tumors. JNK drives the transcriptional induction of mitogenic molecules, matrix metalloproteases and systemic signals that lead to tumor growth, tissue invasiveness and malignancy. Here we review our findings on a tumor-intrinsic, Eiger- and stroma-independent mechanism that contributes to the unlimited growth potential of tumors caused either by chromosomal instability or impaired cell polarity. This newly identified mechanism, which was revealed in an experimental condition in which contacts between tumor cells and wild-type epithelial cells were minimized, relies on interactions between functionally distinct tumor cell populations that activate JNK in a cell-autonomous manner. We discuss the impact of cell interaction-based feedback amplification loops on the unlimited growth potential of epithelial tumors. These findings are expected to contribute to the identification of the relevant cell populations and molecular mechanisms to be targeted in drug therapy.

上皮肿瘤的生长通常由细胞与周围基质的相互作用决定。果蝇在确定介导这些相互作用的相关分子元素方面发挥了作用。值得注意的是，从募集的血细胞释放的TNF配体Eiger在激活上皮肿瘤中JNK肿瘤促进途径方面的作用。JNK驱动有丝分裂分子，基质金属蛋白酶和系统性信号的转录诱导，导致肿瘤生长，组织浸润和恶性肿瘤。在这里，我们回顾我们关于肿瘤内在，艾格峰和基质独立机制的发现，该机制有助于由染色体不稳定或细胞极性受损引起的肿瘤无限增长。这个新发现的机制，是在肿瘤细胞与野生型之间接触的实验条件下揭示的最小化上皮细胞，依赖于以细胞自主方式激活JNK的功能不同的肿瘤细胞群之间的相互作用。我们讨论了基于细胞相互作用的反馈放大环对上皮肿瘤无限增长潜力的影响。这些发现有望有助于药物治疗中相关细胞群的鉴定和分子机制的确定。